More than 1 in 3 U.S. adults have cardiovascular disease. Dietary factors contributed to nearly half of all cardiometabolic deaths in 2012. The DASH-sodium diet is a dietary pattern that is high in fruits, vegetables, and low-fat dairy products and low in sodium, saturated fat, and cholesterol which lowers blood pressure and has also been shown to reduce the risk of hypertension, cardiovascular disease, and mortality. The American Heart Association recommends the DASH-sodium dietary pattern for the prevention of cardiovascular disease. This cost-effective proposal maximizes the scientific value of the existing data and specimens from the multi-center, randomized, controlled DASH-sodium feeding study by conducting high-impact and novel biomarker research. We propose to conduct untargeted metabolomics and targeted assays of mineral metabolism [fibroblast growth factor-23 (FGF-23) and phosphorus] and inflammation [C-reactive protein (CRP) and soluble urokinase-type plasminogen activator receptor (suPAR)] using serum specimens collected at the end of the intervention phase for the low-sodium DASH diet and the high-sodium control diet (N=393). These sodium phases within each dietary pattern were selected to maximize the contrast and to reflect a comparison between the recommended diet for cardioprotection vs. the typical U.S. diet. The specific aims of the research proposal are: 1) to characterize the serum metabolomic fingerprint of the DASH-sodium dietary pattern; 2) to identify serum metabolomic mediators of the blood pressure lowering effect of the DASH-sodium dietary pattern; and 3) to determine the effect of the DASH-sodium diet on intermediate markers of cardiovascular risk (serum levels of FGF-23, phosphorus, CRP, suPAR). The Principal Investigator, Casey M. Rebholz, PhD, MS, MPH, is a K01-funded early stage investigator with a tenure-track position as an Assistant Professor at Johns Hopkins Bloomberg School of Public Health. Preliminary findings in the original DASH feeding study provide compelling support for the current proposal. Collaboration with established investigators in relevant research areas (nutritional epidemiology, biomarkers research, metabolomics, and feeding studies) will catalyze the proposed research. The NHBLI BioLINCC has approved the request for DASH-sodium data and specimens for this proposed research. The proposed research will advance dietary assessment methodology and provide novel insights into diet- modifiable cardiovascular disease pathogenesis with the goal of guiding prevention and therapeutic approaches through diet, to be tested in future grant proposals by Dr. Rebholz. Strengthening the evidence for cardioprotective diets through the proposed research constitutes an opportunity to improve the heart health of millions of Americans.